Currently commercially available materials for biomedical coatings for the above mentioned applications, either synthetic or biological are typically capable of becoming non-flowable once applied onto bodily tissue. These include viscous gels with little or no further curing, as well as compositions that solidify or cure once applied. Cyanoacrylates products such as Ethicon's Dermabond® and Covidien's Indermil® are examples of tissue adhesives that possess high strength and cure in place. These materials polymerize to achieve the strength required, but do not offer the user any control of the degree of curing. Without the control of the degree of curing, they typically address only one clinical need, in this case to close and hold the incisions.
Other products such as Ethicon's synthetic Omnex™ and biological Evicel® and Cryolife's BioGlue® are examples of sealants—that act as a sealant to prevent leakage. Again these materials typically address only one of the four clinical needs of acting as a sealant, acting as an adhesive, acting as a hemostatic agent, or acting as an adhesion preventing coating. Available products do not offer the user the option to change the performance characteristics to address a different clinical need. Products such as Ethicon's Intercoat®, Genzyme's SepraGel®, Confluent's SprayGel®, and Covidien's SprayShield™, to name a few, are examples of adhesion barriers. These are either one of, or a combination of, hydrogels of PolyEthylene Glycol (PEG), Poly Vinyl Alcohol (PVA), CarboxyMethyl Cellulose (CMC), or HyaLuronic Acid (HLA). Once again these materials typically only address one of the four clinical needs already discussed, in this case to act as an adhesions preventative. As before, these materials do not offer user the option to change the performance characteristics to address a different clinical need.
Although there may be some materials with properties mid-way between sealants and adhesion preventatives, their properties are not optimized for either application and they cannot be changed by the surgeon at the time of application during surgery. Many of the solutions that the art provides in the four areas of surgical adhesives, sealants, adhesion preventatives and hemostatic agents are based on cross-linkable systems. Initially flowable to allow application to the surgical site to be treated, the product becomes non-flowable once applied; that is, it stays in place to function properly.
The performance characteristics of the hydrogel products are intimately related to cross-link density. When cross-link density is high, mechanical strength is high and (water) swellabilty is low. High cross-link density hydrogels are often associated with products that function as adhesives. Sealants often require slightly less mechanical strength; therefore hydrogels products in this class category can have cross-link densities that are concomitantly slightly lower. Finally a class of surgical adhesion preventatives based on hydrogel technology is cross-linked at a much lower level than the other two product classes. Their lower cross-link density allows a much greater amount of swellability leading to a very slippery behavior. This latter characteristic has been identified by some to contribute to the ability to prevent viscera from adhering to one another or the initiation of collagen deposition leading to adhesion formations. Likewise, clinically relevant properties of some hemostatic agents depend on the mixing ratios of components. For example, the mixing ratios of fibrinogen and thrombin alter the properties of the resulting matrix.
It is clear that all the products mentioned above offer pre-determined properties to address one clinical need only. There is no flexibility or choice for the physician to alter or dial in the properties for other clinical needs at the time of application during surgery.
There are many patent and open literature references that describe the formation of hydrogels based, wholly or in part, on PEG derivatives. Multi-armed PEGs are of particular interest. They have been made highly reactive when end-capped with electrophilic moieties; they react very quickly, for example, with nucleophilic species such as amines. The nature of these nucleophile-containing materials varies. In one case, they can be proteins, which normally contain an abundance of primary amines and other groups available for reaction. A second strategy is to have the nucleophile-containing material totally synthetic in nature. An example of the latter is a multi-armed PEG in which the arms are terminated in amine groups, especially primary amines. Trilysine is another example of a nucleophile-containing material, a compound that contains four amines, three of which are primary. These two classes of materials, the nucleophiles and the electrophiles, are often presented at the time of application as aqueous solutions of given concentrations. They are initially stored separately to prevent unwanted reaction prior to application.
Important hydrogel properties that can be altered by formulation include mechanical properties (e.g. tensile strength, modulus, elongation-to-break) and adhesive properties (e.g. adhesive and cohesive strength). Biological responses such as tissue reaction, protein deposition, as well as absorbability, can be altered or adjusted. Of particular interest are formulations that can render a hydrogel useful as a surgical adhesive, a surgical sealant, surgical adhesion barrier, or a hemostat. Because of the wide range of formulations available, there is generally a wide range of properties available. However with all these formulations available, one has not been identified that will simultaneously provide the properties necessary to act as an excellent surgical sealant as well as an excellent surgical adhesion preventative. Again, it is an object of this disclosure to specify designs that impart devices to deliver hydrogels with variable selectable-at-time-of-application compositions. Of particular advantage is providing a gradient in the coating orthogonal to the surface of the bodily tissue. In other words, providing a coating comprising a hydrogel which changes in composition, and thus in properties important for the surgical application, as a function of the distance away from the tissue upon which it is applied.
U.S. Pat. Nos. 6,514,534 and 7,025,990 “Methods for forming regional tissue adherent barriers and drug delivery systems” describe methods for forming hydrogel barriers in situ that adhere to tissue and prevent the formation of post-surgical adhesions or deliver drugs or other therapeutic agents to a body cavity. The hydrogels are crosslinked, resorb or degrade over a period of time, and may be formed by free radical polymerization initiated by a redox system or thermal initiation, or by an electrophilic-nucleophilic mechanism, wherein two components of an initiating system are simultaneously or sequentially poured into a body cavity to obtain widespread dispersal and coating of all or most visceral organs within that cavity prior to gelation and polymerization of the regional barrier. The hydrogel materials are selected to have a low stress at break in tension or torsion, and so as to have a close to equilibrium hydration level when formed.
U.S. Pat. No. 6,818,018 “In situ polymerizable hydrogels” discloses compositions and methods for forming hydrogels in situ through a combination of physical and chemical crosslinking processes in which physical crosslinking is mediated by one or more natural or synthetic components that stabilize the hydrogel-forming precursor solutions at a deposition site for a period of time sufficient for more resilient chemical crosslinks to form. Methods of using such hydrogels as tissue coatings to prevent postsurgical adhesion formation, as tissue augmentation or luminal occlusion aids, as matrices for carrying cells, drugs or other bioactive species, as tissue sealants or adhesives, and as medical device coatings also are provided.
U.S. Pat. No. 6,887,974 “Crosslinking agents and methods of use” describes polymeric crosslinking agents that have an inert water soluble polymeric component, biodegradable components, functional components reactive with chemical groups on a protein, for example, amine or thiol groups. The inert polymeric component may be flanked at each end with a biodegradable component which is flanked at each end with a protein reactive functional component. A polymeric crosslinking agent is disclosed having a biodegradable component, polyalkylene oxide, and at least three reactive functional groups that are each capable of forming a covalent bond in water with at least one functional group such as an amine, thiol, or carboxylic acid.
U.S. Pat. No. 7,057,019 “Crosslinked albumin hydrogels” describes materials, methods, and compositions for making crosslinked albumin hydrogels. Embodiments include a biocompatible material of albumin crosslinked with an n-functional crosslinking agent wherein n is at least 3. Other embodiments include a cross-linking agent having a polyalkylene oxide member. Other embodiments include a system for administering an albumin material, the system having albumin and a crosslinking agent that reacts with the albumin to form a crosslinked material made of crosslinked albumin. Another embodiment is a method of making a biocompatible material that includes a step of mixing albumin with an n-functional crosslinking agent wherein n is at least 3.
U.S. Pat. Nos. 6,566,406 and 7,009,034 “Biocompatible crosslinked polymers” disclose biocompatible crosslinked polymers that are formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body.
U.S. Pat. Nos. 7,332,566 and 7,592,418 “Biocompatible crosslinked polymers with visualization agents” disclose biocompatible crosslinked polymers that are formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ. Methods for making the resulting biocompatible crosslinked polymers biodegradable or not are provided, as are methods for controlling the rate of degradation. The crosslinking reactions may be carried out in situ on organs or tissues or outside the body.
U.S. Pat. No. 8,003,705 “Biocompatible hydrogels made with small molecule precursors” discloses biocompatible crosslinked polymers formed from water soluble precursors having electrophilic and nucleophilic functional groups capable of reacting and crosslinking in situ.
U.S. Pat. No. 7,872,068 “Materials formable in situ within a medical device” discloses forming a material in situ by introducing into a space within a patient a water soluble polymer precursor of at least about 10,000 molecular weight solubilized in a flowable aqueous solution. Functional groups on the polymer precursor undergo covalent bonding in situ to form a solid and non-biodegradable material having a swellability of less than about 20% v/v and a Young's modulus of at least about 100 kPa within about 30 seconds to about 30 minutes of initiating a chemical reaction of the functional groups to form the solid material.
U.S. Pat. No. 6,610,033, “Dual component medicinal polymer delivery system and methods of use” discloses apparatus and methods for making and using a medicinal polymer formed from two components. The apparatus includes a double syringe holder housing first and second syringes that is adapted to be coupled with a predetermined orientation to a double vial holder housing first and second vials. The double syringe holder and double vial holder have mating key features that prevent the first syringe from coupling to the second vial and the second syringe from coupling to the first vial. The apparatus also includes a delivery device having first and second inlet ports and a key feature that prevents the first syringe from coupling to the second inlet port and the second syringe from coupling to the first inlet port.
U.S. Pat. No. 7,862,538 “Surgical delivery system for medical sealant” discloses systems for packaging dual or multiple-component adhesive systems that provide enhanced convenience and efficacy. In one aspect, the components of such a system may be divided into containers that allow for foolproof mixing schemes to avoid mixing the wrong components while also providing a sterile surface for mixing materials, with the sterile surface having optimal physical properties for mixing the materials, especially in small amounts. Certain embodiments include a surgical delivery system for a medical sealant including a packaging system with a detachable a sterile surface for mixing the sealant as needed for application.
U.S. Pat. No. 6,165,201 “Method and apparatus for in situ formation of hydrogels” discloses methods and apparatus of forming in situ tissue adherent barriers by using a sprayer capable of applying two or more viscous crosslinkable solutions to tissue. The sprayer comprises separate spray nozzles for each of two or more crosslinkable solutions, wherein each nozzle is either surrounded by an annular gas flow outlet or in communication with a gas-pressurized chamber, and also may include valves that prevent backflow through the supply lines carrying the crosslinkable solutions, and a venting system for venting excess pressure for laparoscopic applications In the presence of gas flow, the crosslinkable solutions are atomized and mixed to form a spray. Multi-component hydrogel systems suitable for use with the inventive methods and apparatus are also described.
U.S. Pat. No. 6,673,093 “Methods and apparatus for in situ formation of hydrogels” discloses methods and apparatus of forming in situ tissue adherent barriers using a sprayer capable of applying two or more viscous crosslinkable components to tissue. The sprayer comprises separate spray nozzles for each of two or more crosslinkable solutions, with each nozzle surrounded by an annular gas flow outlet. Crosslinkable solutions are stored in separate compartments and communicated under pressure to the spray nozzles. In the presence of gas flow through the annular gas flow outlets, the crosslinkable solutions are atomized and mixed in the gas flow to form a spray. Multi-component hydrogel systems suitable for use with the inventive methods and apparatus are also described.
U.S. Pat. No. 7,347,850 “Adhesion barriers applicable by minimally invasive surgery and methods of use thereof” discusses biocompatible crosslinked polymers and methods for their preparation and use with minimally invasive surgery applicators. The disclosure includes compositions and methods for in situ formation of hydrogels using minimally invasive surgical techniques.
U.S. Patent Application No. 20050261782, “Anti-adhesion device” describes a construct that allows opposing tissues to form adhesions with either side of the construct, as part of the natural healing process. The construct however is multi-layered, wherein the space between the layers provides the protection from unwanted adhesions forming between and bonding separate tissues. In one embodiment, this space between layers of the construct may be developed spontaneously, that is the multiple layers are released by design after a finite time and the opposing tissues are free to move independent of each other, free of adhesions. It further discloses an implantable device for the prevention of adhesions comprising a plurality of layers, wherein said plurality of layers comprises at least an anterior layer and a posterior layer, said anterior and posterior layers each having an outer and inner surface, each of said anterior and posterior layers having a porosity comprising a plurality of pores, said porosity varying across the thickness of each of said anterior and posterior layers.
U.S. Pat. No. 7,192,604 “Implantable biodegradable devices for musculoskeletal repair or regeneration” discloses an implantable, biodegradable device, comprising a fibrous matrix, said fibrous matrix comprising first fibers A and second fibers B, wherein fibers A biodegrade faster than fibers B, fibers A and B are present in relative amounts and are organized such that the fibrous matrix is provided with properties useful in repair and/or regeneration of mammalian tissue, wherein one of fibers A and B comprises a biodegradable polymer and one of fibers A and B comprises a biodegradable glass, and wherein the fibrous matrix comprises a gradient structure comprising a transition in the relative concentration of fibers A to fibers B.
Published U.S. Patent Application No. 2012/0045651 “Hydrophobic and Hydrophilic Interpenetrating Polymer Networks Derived from Hydrophobic Polymers and Methods of Preparing the Same” discloses a composition of matter comprising a hydrophobic or hydrophilic (or both) interpenetrating polymer network (IPN) containing a non-ionic/ionic polymer and a hydrophobic thermoset or thermoplastic polymer, articles made from such composition and methods of preparing such articles. The invention also includes a process for preparing a hydrophobic/hydrophilic IPN or semi-IPN from a hydrophobic thermoset or thermoplastic polymer including the steps of placing an non-ionizable/ionizable monomer solution in contact with a hydrophobic thermoset or thermoplastic polymer; diffusing the monomer solution into the hydrophobic thermoset or thermoplastic polymer; and polymerizing the monomers to form a penetrating polymer inside the hydrophobic thermoset or thermoplastic polymer, thereby forming the IPN or semi-IPN. In some embodiments, the non-ionic polymer forms a concentration gradient from a first portion of the composition to a second portion of the composition.
Published U.S. Patent Application No. 2012/0039959 “Anti-Adhesion Alginate Barrier of Variable Absorbance” discloses mono- and bi-layer alginate post-surgical anti-adhesion barriers with tailored absorption profiles and non-migrating characteristics. Muco-adhesive properties of alginates in their solid state are used to localize the device, and lubricious properties of alginates in their liquid state are used to mitigate adhesion formation during wound healing. In addition, the design of the implant can be selected such that the crosslinking agent is released from the device under specific conditions and the absorbance profile modified. A medicinal agent may optionally be incorporated. The application further discloses modification of crosslink density, whereby constructs transition from an adhesive state to a slippery anti-adhesive state as a function of time, or alternatively, the implant is spatially differentiated, and manufactured with two sides of differing crosslink density. Other approaches to varying the properties of an alginate sheet include varying the composition of alginate itself.
PCT Application WO 2000/009074 “VARIABLE OUTPUT APPLICATOR AND METHOD FOR MULTI-COMPONENT BIOLOGIC FLUID AGENTS” discloses applicators for dispensing a range of different tissue sealants, for example fibrin sealants with different setting times, conditioning agents or therapeutic agents, has a manual selector for user easily to select different outputs. Various differential drive mechanisms are disclosed for selectively dispensing, different concentrations of fluids optionally with internal mixing, from two or three or more fluid sources, such as fluid reservoirs carried by the applicator. Interchangeable reservoirs and the option of controlling concentration by discharging one reservoir to waste are also disclosed. The application further discloses a variable output handheld fluid agent applicator for dispensing a multi-component fluid agent to a site of use, the applicator comprising: a) multiple fluid component sources for the multiple fluid components; b) a dispensing tip to deliver the fluid components to the site of use; c) a manually actuated agent delivery system communicating with the multiple fluid component sources to deliver the multiple fluid components to the dispensing tip, and d) a manually operable selector coupled with the agent delivery system to select from available variation in the character of the fluid agent and enable a user to select a desired output; characterized in that the agent delivery system is variable to vary the character of the fluid agent dispensed and the delivery system provides an output of constant character after selection of a desired output.
U.S. Pat. No. 5,240,146 “Variable proportion dispenser” discloses a variable proportion dispenser which includes a housing which houses two pharmaceutical cartridges. A reciprocating drive assembly includes a drive stem extending from the piston of each cartridge, a sliding body mounted to the housing, and two one-way drive devices carried by the sliding body. Each one-way drive device includes a threaded dosage adjuster, and a reciprocating, one-way driver which drives the drive stem into the cartridge. The distance the reciprocating driver can move on the return stroke away from the cartridge is adjustable by changing the threaded position of the dosage adjuster within the sliding body to change if and when the opposed ends of the dosage adjuster and reciprocating driver disengage during the return stroke. During the next delivery stroke, the separated opposed ends do not contact for an initial portion of the stroke. The user can thus control the amount and proportion of each pharmaceutical dispensed during each delivery stroke for each dispensing cycle.
U.S. Pat. No. 5,152,461 “Hand Operated Sprayer With Multiple Fluid Containers” discloses a dispensing device or trigger sprayer which selectively draws fluid out from at least two containers, mixes the fluids in a desired concentration or ratio and expels the mixture of fluids out a nozzle. The trigger sprayer is equipped with a metering device for variably controlling the ratio of the fluids being mixed. The containers or bottles connected to the trigger sprayer are selectively detachable for refilling a container with fluid or exchanging one of the containers with another container having an alternate fluid.
British Patent No. GB 1306126 “HYPODERMIC SYRINGE BODY” claims a hypodermic syringe body for separately storing two components and permitting mixing in the syringe body and dispensing therefrom comprising: a barrel with a distal portion to receive a dispensing means, said barrel having at least two co-extensive channels in the wall thereof and parallel to the axis of the barrel, the ends of said channels being spaced from the ends of the barrel; a piston slideably mounted within said barrel and of axial length shorter than the axial lengths of the channels and positioned to separate said barrel into two non-communicating chambers said piston having a dose sliding fit in said barrel and when adjacent to said channels permitting ready flow of a liquid therethrough, the channels being of dimensions permitting ready flow of a liquid past the piston; a rupturable hermetic seal of a polymeric material applied to seal the piston to the barrel and resistant to rupture except by rotation of the piston; a plunger positively locked to said piston, extending proximal thereof; a plug at the proximal end of the barrel through which said plunger extends, said plug and said plunger being constructed to permit rotation of at least said plunger in said barrel; a hermetic seal between said plunger and said plug; and a hermetic seal between said plug and said barrel, at least one of said last two seals being a rupturable seal of a polymeric material applied to form said seal.
U.S. Pat. No. 4,735,616 “Arrangement for applying a tissue adhesive” discloses an arrangement for applying a tissue adhesive based on human or animal proteins, to seamlessly or seam-supportingly connect human or animal tissue or organ parts by uniting with blood-clot-promoting coagulation factors (thrombin). The arrangement includes a plurality of syringe bodies commonly actuatable by pistons and to which a connecting head is attachable. The syringe bodies have equal effective strokes, yet one of them, i.e., that destined to contain the protein solution, has a cross sectional area that is two to nine times larger than the other one(s). There may be applied tissue adhesives having a fibrinogen content of from 2 to 12%.
U.S. Pat. No. 8,088,099 “Fluid dispenser” discloses dispensing assemblies, methods, and kits of parts for dispensing two separate fluids to an treatment site, including entraining non-atomized flow of a first fluid in an atomized flow of a second fluid, delivering a first fluid upstream from a second fluid, delivering a first fluid and a second fluid with re-shapeable malleable tubes, delivering first and second fluids with releasable connectors maintained by a handle assembly, and kits of parts with angularly offset pockets.
U.S. Pat. No. 7,959,612 “Dual syringe injector system” discloses devices and methods for simultaneous injection or delivery of two or more substances from separate syringes. The syringes are loaded into a device that has a handle and a screw driven mechanism for simultaneously depressing the plungers of the syringes. The user grasps the handle and positions the device. Thereafter, the screw mechanism is used to simultaneously advance the plungers of the syringes thereby simultaneously expelling the substances from the syringes.
U.S. Pat. No. 6,939,329 “Apparatus for holding and operating one or more syringes” discloses an apparatus for supporting a syringe which includes a handle portion and a cradle. A clip is provided for connecting the plungers of two or more syringes, and two or more syringes are operated by placing one in the cradle and attaching the clip to the plungers for simultaneous operation of the plungers. The handle portion also forms a cavity for storing the clips. The apparatus is preferably used in combination with an applicator tip that combines the outputs from the two or more syringes.
Published U.S. Patent Application No. 2009/0062741 “Dual lumen syringe” discloses a dual lumen syringe which includes a body having a pair of elongate cavities or lumens formed therein. A directional valve is associated with each lumen. The valve is alternated between the first position wherein the lumen is communicably connected to a fluid inlet and a second position wherein the lumen is connected with a fluid outlet. There are a pair of elongate plungers, which are fixedly interconnected by a handle. Each plunger is received and longitudinally slidable in a reciprocating manner through a respective lumen. The valves are switched to a first position wherein the lumens are interconnected with the fluid inlets and the plunger is refracted to aspirate fluids through the respective inlets and into the lumens. The valves are then switched to a second position to communicably interconnect the lumens with the outlets. The plungers are then simultaneously driven inwardly through the respective lumens to drive the fluids simultaneously through the outlets to a dispensing tip permanently connected to the body and in communication with the outlets.
U.S. Pat. No. 5,599,312 “Syringe” claims a syringe comprising: a cylinder, having a connection portion for a syringe needle at a first end and an opening at a second end; and a plunger to be inserted into the cylinder from the opening, wherein a plurality of partitions are slidably provided between said connection portion and said plunger within said cylinder to divide an internal space of said cylinder into plural watertight chambers, wherein between adjacent partitions or between one of said partition and said plunger, two or more chambers are formed, wherein the chambers are filled with respective injection agents, and a passage formed integrally with the cylinder and communicating each of said chambers with said connection portion is provided without distorting said partitions when said plunger is moved within said cylinder toward said first end.
U.S. Pat. No. 3,477,431 “COMBINED MIXING SYRINGE AND CONTAINER”, claims a combined syringe and plural compartment container comprising: an elongated syringe barrel having a delivery end and an open end and an enlarged portion of greater diameter than the syringe barrel extending around its periphery at a point intermediate its ends; a plunger slidably disposed within said syringe barrel, said plunger having at least one piston affixed thereto, the piston slidably and sealingly engaging the syringe barrel and defining, with the syringe barrel, at least one compartment on either side of said enlarged portion of the syringe barrel; sealing means closing the delivery end of the syringe barrel; a cover closing the open end of the syringe barrel, said cover having an opening therein, the plunger extending through said opening in the cover and having a slot in the shaft thereof immediately adjacent to the cover when the plunger is in the extended position.
U.S. Pat. No. 8,454,559 “Hypodermic syringe with retractable needle” discloses hypodermic syringe having a barrel which with an inner wall thereof defines a reservoir, a closing-off device near the first end of the barrel, and a plunger that is movably placed in the second end of the barrel, wherein the closing-off device comprises a circumferential wall that sealingly abuts the inner wall of the barrel, at the side facing away from the nozzle is provided with a recess extending along a centre line of the closing-off device and over the full width thereof, which recess merges into the through-opening, with in the recess two diametrically opposite flexible locking members, extending in the longitudinal direction of the recess and towards the inner wall, which locking members engage into diametrically placed locking grooves in the inner wall, and at the side facing away from the nozzle, at a circumferential part of the closing-off device situated outside of the recess, is provided with two diametrically opposite and radially outwardly extending blocking members, that engage in diametrically placed blocking grooves in the inner wall.
U.S. Pat. No. 7,351,224 “Retractable syringe assembly designed for one use” discloses a syringe assembly having a retractable needle, the syringe assembly being rendered unusable after a single injection and having a hollow syringe body, a retraction mechanism with a spring disposed in the front portion of the syringe and an inner head, a continuous retainer member surrounding the inner head, and a bridging portion disposed between the continuous retainer member and the inner head, wherein the bridging portion couples the continuous retainer member and the inner head to form a fluid seal between a fluid passageway and the barrel prior to retraction, and a plunger reciprocally disposed inside the barrel and forming a variable chamber between the plunger and the needle holder prior to and during retraction, wherein the continuous retainer member is releasable from the inner head of the needle holder when the plunger is further depressed inside the barrel following injection.
Japanese Patent Application JP59028949 “APPARATUS FOR SAMPLING BLOOD” discloses a device for blood sampling or for use as a hypodermic syringe consists of a holding arrangement for receiving syringe barrels of varying size and has a metering facility which makes it possible for different metering volumes to be set for drawing-up of a reagent. The holding arrangement for receiving syringe barrels of varying size is, in a first embodiment, provided with several rings running concentric to one another and to which syringe barrels of varying diameter can be attached, and, in a second embodiment, with several parallel slots into which syringe barrels of varying diameter and size can be inserted by means of flange sections. The facility for metering adjustment has a unit with guide curves and cams which can be adjusted relative to one another and, as a function of their setting, limit the movement of the plunger in the direction of the opening of the syringe barrel for receiving the point of the needle.
U.S. Pat. No. 5,477,987 “DISPENSING APPLIANCE FOR AT LEAST TWO COMPONENTS” discloses a dispensing appliance for at least two components which comprises a respective pump assembly for each component, each of said pumps being connected to a detachable container holding one of said components, and the pump outlets ending in a common but divorced outlet. Said pump assemblies are held in a frame which can be dismantled and reassembled, and the cylinders of said pump assemblies are composed of different segments.
U.S. Pat. No. 5,656,035 “REFILLABLE FIBRINOGEN DISPENSING KIT” discloses a refillable dispenser for separately dispensing each of two biological fluids contained therein for intermixing at a site outside of the dispenser to produce hemostasis or a tissue adhesive. The dispenser is compact, contains integrally formed internal reservoirs for the two biological fluids, an injection port on each reservoir for refilling the reservoir, and is designed for efficient filling without compromising the integrity of the sterile field. The dispenser is capable of dispensing the biological fluids, such as fibrinogen and thrombin, at either a focused point or in an aerosol mist In addition, spray elements are disclosed for uniformly distributing the two biological fluids along either the interior surface or the exterior surface of an implantable vascular graft.
U.S. Pat. No. 4,355,739 “Liquid storage container” discloses a liquid storage container that can be connected or attached to a spray pump which comprises two separate chambers to hold liquid components, each chamber having a take-up tube which leads to a mixing chamber contained within a movable member attached to a movable external selector, the member having openings therein, wherein, when the external selector is moved, the movable member attached thereto moves in a manner such that the ratio of the quantities of liquid components from the chambers varies.
U.S. Pat. No. 5,402,916 “Dual chamber sprayer with metering assembly” discloses a hand-actuated multiple-container trigger sprayer includes a sprayer head assembly removably connected to a plurality of fluid containers. The sprayer head assembly has an outer housing, a nozzle attached to the housing, pump mechanism enclosed within the housing, and tubing fluidly connecting each of the plurality of fluid containers with the pump mechanism in the housing. A trigger or lever actuates the pump mechanism to draw fluid through the tubing from each of the plurality of fluid containers and to discharge the fluid through the nozzle. A metering device is located between the fluid containers and the pump mechanism and is accessible externally from the housing to selectively control the amount of fluid drawn from the containers. The metering device includes flow paths to the pump mechanism for each of the fluid containers. The diameter and length of at least one of the flow paths can be controlled to selectively control the amount of fluid drawn from the fluid containers. The metering device within the spray head assembly allows user-selected ratios of fluid to be drawn from the containers and sprayed through the nozzle in the spray head. The patent further references examples of multiple-container trigger sprayers, U.S. Pat. Nos. 3,786,963; 4,355,739; 5,152,431.
U.S. Pat. No. 7,997,449 “Fluid delivery system for dispensing primary and secondary fluids” discloses a trigger operated fluid delivery system for dispensing two different fluids is disclosed. The fluid delivery system includes a first container having a first primary fluid, a fluid inlet conduit in fluid communication with the first container, and a pump for drawing the first fluid through the fluid inlet conduit and into a pump chamber. A fluid discharge conduit is located downstream of the pump chamber. The fluid discharge conduit is in fluid communication with the pump chamber and a discharge orifice. The pump discharges the first fluid from the pump chamber into the fluid discharge conduit. The fluid delivery system also includes a second container having a second fluid that delivers the second fluid into the fluid discharge conduit. The second fluid mixes with the first fluid when the first fluid is discharged into the fluid discharge conduit such that a mixture of the first fluid and the second fluid is discharged through the discharge orifice.
U.S. Pat. No. 3,303,970 “Device for simultaneously dispensing from plural sources” discloses improved mechanism for simultaneously dispensing several liquids; improved mechanism for varying the proportions of the several liquid constituents in the mixture before or during the dispensing operation; mechanisms having novel valve means for metering predetermined proportions of several liquids which are being simultaneously dispensed; and improved dispenser which permits varying the proportions of a dispensed liquid mixture to achieve optimum results.
U.S. Pat. No. 4,826,048 “Dispenser for manually discharging plural media” discloses a dispenser that has two facing and outwardly sealed reservoirs for separate media components, as well as for each reservoir a separate discharge pump, both discharge pumps being simultaneously operable by means of a common handle. The components are separately sucked in and are kept separate up to a mixing zone located inside or outside the handle, but with respect to the use thereof are brought together at the latest possible time. The components can be brought together in a precisely dosed quantity ratio.
U.S. Pat. No. 4,993,594 “A multi-constituent mixing and metering dispenser” discloses a multi-constituent mixing and metering dispenser adapted to yield a composition whose intermixed constituents are in relative proportions settable by the user. The extrudable constituents are stored in separate compressible pouches encased in face-to-face relation in the squeeze container of a supply section. Secured to the top of the container is a metering and mixing output section having a mixing chamber therein provided with an outlet. Each pouch has a flexible dip tube inserted therein leading to the mixing chamber in the output section. The container includes a check valve that is caused to close when the container is squeezed, thereby hermetically sealing the container and exerting pneumatic pressure on the pouches to cause extrusion of the constituents into the mixing chamber from which the resultant mixture is discharged through the outlet. Mounted in advance of the mixing chamber is a metering mechanism having a dial-turned shaft on which a series of cams is supported, each acting to pinch a respective tube to restrict flow of the related constituent into the mixing chambers. The cam arrangement is such that in the course of a full turn of the dial by the user, the relative proportions of the constituents are varied through a broad ratio range to produce a composition whose effective strength or other characteristic can be set by the user from a predetermined minimum value to a maximum value.
U.S. Pat. No. 5,152,461 “Hand operated sprayer with multiple fluid containers” discloses a dispensing device or trigger sprayer which selectively draws fluid out from at least two containers, mixes the fluids in a desired concentration or ratio and expels the mixture of fluids out a nozzle. The trigger sprayer is equipped with a metering device for variably controlling the ratio of the fluids being mixed. The containers or bottles connected to the trigger sprayer are selectively detachable for refilling a container with fluid or exchanging one of the containers with another container having an alternate fluid.
European Patent publication EP1022060 A2 “Method and apparatus for dispensing multiple-component flowable substances” discloses a sprayer apparatus for selectively spraying or dispensing multiple fluid components. The apparatus comprises a housing having a first inlet and a first outlet, the first housing inlet being adapted for attachment to a garden hose, the first housing outlet being in fluid communication with the first housing inlet; and an insert member having a first inlet for receiving fluid and a first outlet for dispensing fluid therefrom, the first insert inlet being in fluid communication with the first insert outlet through a passage defined by the insert member, the insert member being mateable with the housing so that the first housing outlet mates with the first insert inlet so that a fluid can flow from the first housing inlet to the first insert outlet. A method of spraying a fluid is also disclosed.
U.S. Patent publication No. 2013/0075428 “Dispenser” discloses a dispenser that provides measured doses of at least two components using a common pump. Each of the components is stored in its own separate container; each of which is connected to the common piston pump through an inlet valve. A metering device is disposed between the inlet valves and the pump chambers. The metering device is rotatable around an axis and controls the volume of each component disposed by either changing to flow rate of the component through its inlet valve or by changing the stroke length of the piston associated with its inlet valve. Preferably, the metering element is connected in a non-rotation manner (e.g. in form of a four cornered shaft) to the piston and the dispenser head, such that the adjustment of the desired dosage ratio is easily done by turning of the dispenser head. For a simple structure, the metering element includes holes or recesses of different size or a bent slot for changing the flow section and/or the flow length in an easy way. It is also possible to change the cross section of the respective inlet valve by a simple limitation of the respective valve opening.
U.S. Pat. No. 5,385,270 “Selectable ratio dispensing apparatus” discloses an apparatus for dispensing two flowable substances in a user selectable ratio having a container and a selector member. The container includes a dispensing end, a flexible continuous outer wall, and a flexible inner diaphragm separating the container into two generally equal chambers for each receiving a different flowable substance. Each of the chambers includes an end generally open proximate the dispensing end of the container. The selector member is disposed between the open ends of the chambers and the dispensing end of the container and includes a single opening extending therethrough. The selector member is selectively rotatable with respect to the container between a series of predetermined positions where the selector member opening is either in full registry, partial registry or not in registry with the open ends of each of the chambers such that upon compression of the outer container wall, a predetermined measure of flowable substance is dispensed from the dispensing end of the container with the ratio of the flowable substance from the two chambers which constitutes the predetermined measure being selectively variable.
U.S. Pat. No. 6,036,057 and PCT publication WO1997/026086 “Dual piston variable proportioning system” discloses a proportioning system which includes first and second cylinder and piston arrangements with an actuator operably engaging the first and second cylinder and piston arrangement. By changing the diameter and/or stroke of the pistons the mix ratio of two dispensed fluids changes. By changing the pivot point of the actuator, the stroke length can be changed. The proportioning system also includes a safety mechanism which prevents a concentrated fluid from being dispensed should the reservoir of diluting fluid be depleted. The embodiments provide for adjusting the proportioner to affect the mix ratio of the several fluids which are being mixed together and configurations for changing the proportioning ratios.
U.S. Pat. No. 5,009,342 “Dual liquid spraying assembly” discloses a dual liquid spraying assembly comprises an outer container containing at least two separate compartments for two different liquids, a spray pump dispenser for mounting on the outlet of the container, and a valve assembly mounted between the compartments and the spray pump dispenser for controlling the proportions of the different liquids dispensed. The valve assembly comprises an inner valve member having a discharge outlet for connection to the spray pump dispenser and at least two inlets for connection to the respective compartments, and an outer, control sleeve rotatably mounted on the inner valve member for controlling connection of the inlets to the outlet. Both the inner and outer valve members are releasably secured on the outlet of the container to extend co-axially with the outlet opening. Movement of the control member relative to the first valve member between the first and second positions gradually varies the relative sizes of the two inlets so as to vary the ratio of the two liquids dispensed.
U.S. Pat. No. 4,838,457 “Lotion blending and dispensing unit” discloses a lotion blending and dispensing unit for internally combining and then discharging a composite lotion or solution which includes a cylindrical housing having a storage chamber for enclosing at least a pair of lotion containers removably mounted on a mounting block. The block is provided with at least a pair of orifices on an annular surface having a central projection about which a selector dial rotates. The projection includes at least a pair of passageways in fixed alignment with the orifices so as to conduct lotion therethrough. A regulating disc is movably disposed on the annular surface for revolving about the projection whereby a plurality of different sized apertures may be selectively aligned between the orifices and the passageways. The disc is movable in response to rotation of the selection dial.
U.S. Pat. No. 4,432,469 “Device for discharging a plural-component material” discloses a device for discharging measured amounts of a plural-component material, such as an adhesive, filling, sealing or putty-like substance includes an axially extending casing having a first end. The interior of the casing is divided into separate compartments each having a discharge opening at the first end. A mixing chamber is positioned at the first end of the casing for receiving the components discharged from the compartments. A slide plate is positioned between the first end of the casing and the mixing chamber and is rotatable about the axis of the casing. The slide plate has openings for passageways alignable with the discharge openings for admitting selective amounts of the components into the mixing chamber. Due to this arrangement, the mixing ratio of the two components, contained in the compartments 1a, 1b can be changed in the adjustment position bordering the locking position. The mixing ratio of the components also influences the hardening time of the resulting mixed substance.
U.S. Pat. No. 5,634,571 “Apparatus for dispensing two sprayable substances in a user selectable ratio” discloses an apparatus for dispensing two sprayable substances in a user selectable ratio. The dispensing apparatus comprises first and second pressurized containers for holding first and second sprayable substances. The dispensing apparatus further includes a manifold member having first and second inlet openings and an outlet opening. The inlet openings receive the dispensing ends of the first and second pressurized containers. The manifold member includes two passages which are in fluid communication between the first and second inlet openings and the outlet opening, respectively. A selector member having a single opening extending therethrough is provided in fluid communication with the first and second passages in the manifold member. The selector member is selectably rotatable with respect to the outlet opening in the manifold member. An actuator is provided for dispensing the sprayable substance from the apparatus with the ratio of the dispensed substance being selectably variable by the user from 100% of the first sprayable substance and 0% of the second sprayable substance in the first position to 0% of the first sprayable substance and 100% of the second sprayable substance when the selector member is in the second position, to any desired ratio therebetween when the selector member is in an intermediate position.
U.S. Pat. No. 6,464,107 “Dosage dispenser” discloses a proportioning dispenser for proportioning at least two components which are each supplied via a pump unit from an associated accommodating compartment is disclosed. The adjustment of the mixing ratio is effected via a transmission member the point of application of which is adjustable with respect to the two pump units. The actuation of the pump units is performed by a pivotable or displaceable transmission member the pivoting axle of which can be displaced relative to the operating members of the pump unit—for example the displacers. The position of the pivoting axle relative to the pump units is in this case selected to effect a change in the opposite direction, such that only the proportioning ratio of different components relative to one another is adjusted while the complete capacity preferably remains essentially constant. It is also conceivable, however, to adjust the complete displacement volume by adjusting the pivoting axle. Both components can be dispensed in a mixed or unmixed condition.
U.S. Pat. No. 5,224,627 “Metering pump dispenser for liquid and/or pasty media” discloses a metering pump dispenser that serves for simultaneous metered output of liquid and/or pasty media from at least two separate supply chambers, which are arranged in a common pump housing and to which are assigned individual separate metering pumps, each with an intake and output valve. The metering pumps are manually driven by a common actuating device, which extends on the side of actuation in a common front side of the metering pumps that are present and is provided with one or more output channels. Metering pumps each have as pump devices communication bellows which are joined on the housing side with pump housing and on the output side with the common actuating device. Actuating device is a lever-type device mounted in a swiveling manner around a swivel seat on one side in a head part of pump housing axially projecting over supply containers, for conducting limited pump strokes. Swivel axis of swivel seat is arranged crosswise to a common plane of symmetry of metering pumps, so that metering pumps have variable distances and variably large actuation levers to the swivel axis, and upon actuation of actuating device, pump strokes of different magnitude can be introduced in a specific, preselectable ratio at the same time and in the same direction.
U.S. Pat. No. 5,848,732 “Dispenser for a liquid medium consisting of two components” discloses a dispenser for a liquid medium consisting of two components. The dispenser in particular comprises two accommodation compartments for two different components of the material to be dispensed. Each of the accommodation compartments has an outlet and a mixer connected thereto. The mixer is manually adjustable by an adjuster and changes the ratio of the supplied components of the medium. Finally, the dispenser comprises a dispenser nozzle for the medium to be dispensed, which is connected to the mixer.
Japanese patent publication JP 54,137,703 “LIQUID RATIO VARIABLE CONSTANT CAPACITY DISCHARGE SYSTEM” discloses a system that targets making constantly optional miscible ratio adjustable by only necessary amount in the mixing material at high efficiency in such a way that fluidic material may be measured at optional ratio by easier operation giving facility for discharging it at constant amount. Crude material reservoirs are respectively connected through supply pipes to discharge devices which constitute a plunger pump. The discharge devices are equipped respectively with needle valves at intake ports and discharge ports and its hollow part has plungers respectively connected to one lever.
European patent publication EP 1,433,533 A1 “Dispensing apparatus having means for dispensing two products in variable ratios” discloses a dispenser for two fluid products in variable proportions that has two containers with separate pumps, push-button with outlet valve and regulator. The dispenser consists of two containers with separate pumps operated by a push-button with an outlet valve. The pushbutton is connected to the pumps by at least one flexible transmission member and a control element that can be adjusted by a regulator to set its end position and vary the proportions in which the products are dispensed from the containers according to the user's requirements.
U.S. Pat. No. 7,222,752 “Dispenser device including means that enable two substances to be dispensed in varying proportions” discloses a dispenser device that includes reservoirs for containing respective substances, pumps associated with respective reservoirs, and a pushbutton. The device allows two substances to be dispensed in varying proportions by actuating the pushbutton. In embodiments, each pump has a moving control member which, when actuated, causes the substance contained in the reservoir associated with the pump to be dispensed. In embodiments, at least one elastically-deformable transmission member is associated with a control member and is disposed in such a manner as to transmit displacement of the pushbutton to the control member in order to dispense substance. In embodiments, at least one adjustment member adjusts the end-of-stroke position of the displacement at least of the control member associated with the transmission member.
U.S. Pat. Nos. 7,686,191 and 6,968,982 “Multiple-mist dispenser” disclose dispenser that includes at least one container and at least one nozzle for dispersing the contents of the container(s). In one preferred embodiment, first and second nozzles functionally associated with sterilization agent within the container are positioned to disperse the sterilization agent to first and second target points respectively, the first target point being distinct from the second target point. In another preferred embodiment of the present invention, a grid is positioned in front of the nozzle(s) so that a dispersement of sterilization agent from within the container(s) sterilizes the grid(s) when the nozzle(s) are activated. Yet another preferred embodiment of the present invention is directed to a multiple-mist dispenser that includes a dual chamber activation sleeve so that two nozzles are simultaneously actuatable by depression of the dual chamber activation sleeve.
PCT publication WO2008/053311 “A SPRAYING DEVICE WITH LIQUID ADJUSTMENT MECHANISM” discloses a sprayer which comprises a spraying mechanism, at least two liquid containers, a liquid adjusting mechanism, and liquid feeding members; the spraying mechanism having a knob for activating a pump or releasing a valve for dispensing a liquid coming from an inlet to an outlet; the liquid feeding member has at least two liquid feeding tubes, one end of each of the at least two liquid feeding tubes is in liquid communication with each of the at least two liquid containers respectively, and the other end of each of the at least two liquid feeding tubes is jointed and connected to the inlet of the spraying mechanism; the liquid adjustment mechanism comprising two sets of adjoining sloped surfaces and sets of rollers are in contact with the two flexible portions of each of at least two liquid feeding tubes and when moving from right to left change sectional areas of the inside space of the flexible portions in such a way that amount of liquid supplied from each of the at least two liquid containers through each of the at least two liquid feeding tubes is adjusted. When flow of liquid from one feeding tube increases by the adjusting mechanism, the flow from the other feeding tube decreases in a way that the total amount of the liquid supplied by at least the two feeding tubes are substantially constant. In practice it is possible to mix two liquids such as two different perfumes with different fragrances or mix two different color paints to create a new fragrance and or paint color.
U.S. Pat. No. 6,299,023 “Device for dispensing two substances in a user selectable ratio with replaceable cartridges” discloses a device for dispensing a base substance and a booster substance in a user selectable ratio includes a dispenser head having a pair of spaced apart outlet ports, a first cartridge containing the base substance which is removably coupled onto the dispenser head and a second cartridge containing the booster substance which is removably coupled onto the dispenser head. Each of the first and second cartridges includes a collapsible plastic liner which is mounted onto a supporting frame, the supporting frame of each cartridge having a uniquely shaped flange. A first pump assembly is disposed within the dispenser head and serves to draw a fixed amount of the base substance from the first cartridge and dispense the fixed amount of base substance out one of the outlet ports upon depression of a trigger which is slidably disposed in the dispenser head. A second pump assembly is disposed within the dispenser head and serves to draw a fixed amount of the booster substance from the first cartridge upon depression of the trigger, dispense a user selectable percentage of the fixed amount of booster substance out the other outlet port and return the remaining percentage of the fixed amount of the booster substance back into the second cartridge.
U.S. Pat. No. 7,021,499 “Aerosol package” discloses an aerosol spray cleaner comprises two containers and a dispenser with a single dispensing spray outlet. One container has a cleaning composition and the other has an oxidizing composition. An integrally molded actuator includes a resiliently cantilevered lever connected to container valves to simultaneously open the valves to dispense the two fluids through the dispensing spray outlet. A handle extends laterally of the containers so grasp the handle and depress the actuator with a thumb. It further references manual trigger dispensers which are disclosed in U.S. Pat. Nos. 5,332,157, 4,862,052, 4,821,923 and 4,432,469.